The focus of this project is to examine physiological mechanisms that regulate human skeletal muscle growth. Muscle wasting is a common phenomenon in many conditions, such as cancer, AIDS, trauma, sepsis, kidney failure, and is also particularly prevalent in the elderly. The loss of muscle mass leads to overall weakness, immobility and physical dependence, and can be responsible for an impaired response to stress, which is associated with higher mortality rates during infection, surgery, and trauma. Nutrition and resistance exercise are two major protein anabolic stimuli for skeletal muscle. Our general hypothesis is that the magnitude of the protein anabolic response will be determined by the reciprocal interactions between these two stimuli. In particular, we propose that skeletal muscle protein accretion is dependent upon both the timing of the nutritional stimulus in relation to the exercise bout and the amount of energy provided by the nutritional stimulus. We further hypothesize that the muscle protein anabolic response following a nutrient stimulus or muscular contraction will be more pronounced in healthy young men than in young women. Specific aims: (1) To determine the magnitude of the acute response of skeletal muscle protein synthesis and net protein anabolism to a nutritional stimulus given before or after a bout of resistance exercise. (2) To determine the magnitude of the acute response of skeletal muscle protein synthesis and net protein anabolism to a nutritional stimulus providing an amount of energy that either matches or exceeds the exercise-induced energy expenditure. (3) To determine the differences between women and men in the response of skeletal muscle protein synthesis, efficiency of amino acid utilization for protein synthesis, leucine oxidation, and net protein anabolism to resistance exercise alone and in combination with a nutritional stimulus delivered before or after a bout of resistance exercise. Significance. These studies will provide insight into physiological mechanisms that regulate human muscle protein balance, and will be utilized as a basis from which to develop scientificallybased interventions for improving muscle protein balance in conditions such as aging, trauma, cancer, and AIDS.